The use of dipeptides as source for certain amino acids as component of mixtures or solutions for artificial nutrition is known (see European patent EP-B-0 087 750, German patent DE-C-31 08 079 and European patent EP-A-0 182 356). The use of such dipeptides is especially appropriate if the free amino acids to be administered are poorly soluble in water, such as cystine, tyrosine, tryptophane, valine, leucine or isoleucine, or are not stable in aqueous solution, such as glutamine or cysteine.
The use of dipeptides of glutamine as a component of culture media for cell cultures is also known (see European patent EP-A-0 220 379).
Both infusion solutions and culture media for cell cultures must be used in a sterile form. The simplest and most commonly employed possibility for sterilization is the brief heating of the ready solutions to a temperature of 120.degree. C. The known dipeptides can cyclo-condense to 2,5-diketopiperazines under these conditions, and this can occur even during a fairly long storage.
However, it is known that such 2,5-diketopiperazines exhibit a higher tendency to epimerize than the corresponding linear dipeptides (J. Am. Chem. Soc., vol. 108 (1986), pp. 7327-7332). The presence of the corresponding stereoisomeric 2,5-diketopiperazines must consequently always be considered and dealt with, when using dipeptide solutions, about whose physiological effects no experiments have been previously made in most instances.
It is also known that infusion solutions can use as source for certain amino acids the corresponding N-acetyl derivatives, which are, however, only utilized to an incomplete extent biologically. The cleavage both of N-acyl amino acids as well as of certain dipeptides takes place primarily in the kidneys (Metabolism, vol. 35 (1986), pp. 830-836; Z. Ern ahrungswiss. 21 (1982), pp. 21-26). In addition, dipeptides are also cleaved in the blood plasma.
EP-A-0 267 179 suggested using corresponding N-acyl peptides, e.g. bis-(acetylglycyl)-L,L-cystine, in nutrient compounds as a replacement for the thermally unstable di-and tripeptides of cystine. However, experiments with rats have shown that bis-(acetylglycyl)-L,L-cystine is not suitable as a cysteine source in parenteral nutrition (Z. Ern ahrungswiss. 28 (1989)., pp. 32-35).